Luca Scorrano

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Luca Scorrano
Born (1971-09-06) September 6, 1971 (age 52)
Italy
CitizenshipItalian
Alma materUniversity of Padova
Scientific career
InstitutionsUniversity of Padova

Veneto Institute of Molecular Medicine

University of Geneva
Academic advisors Stanley J. Korsmeyer

Luca Scorrano (born September 6, 1971) is an Italian biologist and professor of Biochemistry at the University of Padua as well as the former Scientific Director of the Veneto Institute of Molecular Medicine in Italy. [1] He is known for his important contributions to the field of mitochondrial dynamics and the interface between mitochondria and the endoplasmic reticulum.

Contents

Biography and research

Scorrano obtained his M.D. and Ph.D. from the University of Padua Medical School in 1996 and 2001, respectively. He then moved to Boston where he worked with Stanley J. Korsmeyer at Harvard Medical School. It is during his postdoctoral work in Korsmeyer's lab that Luca became passionate about mitochondrial dynamics and discovered that mitochondrial cristae remodeling was involved in cytochrome c release and apoptosis. [2] In 2003 he returned to Italy to establish his lab at the University of Padua, and then in Geneva (Switzerland) where he was Professor at the Dept. of Cell Physiology and Metabolism. In 2013 he returned to his native Italy where he continued to unravel the molecular mechanisms of mitochondrial dynamics and their pathophysiological consequences.

He has been prolific in his contributions to the fields of apoptosis and mitochondrial pathophysiology, [3] [4] [5] as well as mitochondrial dynamics and interorganellar contact sites. His lab identified the role of Opa1, optic atrophy protein 1, in holding mitochondrial cristae junctions tight, [6] [7] which is an important determinant of mitochondrial respiratory efficiency. [8] His lab also found augmentation of Opa1 to correct mitochondrial diseases and blunt muscular atrophy, [9] stroke and heart ischemia. [10] In 2008, Scorrano's lab identified Mfn2, a protein mutated in a peripheral neuropathy, as the first molecular bridge between endoplasmic reticulum and mitochondria. [11] His notable work contributed to the current understanding of how mitochondrial shape and structure influence cellular processes and cellular homeostasis. [12] [13]

His lab is now focused on understanding the molecular mechanisms and pathophysiological consequences of mitochondrial dynamics and contacts with the ER in health and disease.

Awards

Scorrano received several prizes and awards, including the Eppendorf European Young Investigator, the Chiara D’Onofrio and the ESCI Award. He is an EMBO Member and sits in several Committees, Advisory and Editorial Boards.

Related Research Articles

<span class="mw-page-title-main">Cytochrome c</span> Protein-coding gene in the species Homo sapiens

The cytochrome complex, or cyt c, is a small hemeprotein found loosely associated with the inner membrane of the mitochondrion where it plays a critical role in cellular respiration. It transfers electrons between Complexes III and IV. Cytochrome c is highly water-soluble, unlike other cytochromes. It is capable of undergoing oxidation and reduction as its iron atom converts between the ferrous and ferric forms, but does not bind oxygen. It also plays a major role in cell apoptosis. In humans, cytochrome c is encoded by the CYCS gene.

<span class="mw-page-title-main">Crista</span> Fold in the inner membrane of a mitochondrion

A crista is a fold in the inner membrane of a mitochondrion. The name is from the Latin for crest or plume, and it gives the inner membrane its characteristic wrinkled shape, providing a large amount of surface area for chemical reactions to occur on. This aids aerobic cellular respiration, because the mitochondrion requires oxygen. Cristae are studded with proteins, including ATP synthase and a variety of cytochromes.

<span class="mw-page-title-main">Bcl-2</span> Protein found in humans

Bcl-2, encoded in humans by the BCL2 gene, is the founding member of the Bcl-2 family of regulator proteins that regulate cell death (apoptosis), by either inhibiting (anti-apoptotic) or inducing (pro-apoptotic) apoptosis. It was the first apoptosis regulator identified in any organism.

Dominant optic atrophy (DOA), or autosomal dominant optic atrophy (ADOA), (Kjer's type) is an autosomally inherited disease that affects the optic nerves, causing reduced visual acuity and blindness beginning in childhood. However, the disease can seem to re-present a second time with further vision loss due to the early onset of presbyopia symptoms (i.e., difficulty in viewing objects up close). DOA is characterized as affecting neurons called retinal ganglion cells (RGCs). This condition is due to mitochondrial dysfunction mediating the death of optic nerve fibers. The RGCs axons form the optic nerve. Therefore, the disease can be considered of the central nervous system. Dominant optic atrophy was first described clinically by Batten in 1896 and named Kjer’s optic neuropathy in 1959 after Danish ophthalmologist Poul Kjer, who studied 19 families with the disease. Although dominant optic atrophy is the most common autosomally inherited optic neuropathy (i.e., disease of the optic nerves), it is often misdiagnosed.

<span class="mw-page-title-main">Apoptosis regulator BAX</span> Mammalian protein found in Homo sapiens

Apoptosis regulator BAX, also known as bcl-2-like protein 4, is a protein that in humans is encoded by the BAX gene. BAX is a member of the Bcl-2 gene family. BCL2 family members form hetero- or homodimers and act as anti- or pro-apoptotic regulators that are involved in a wide variety of cellular activities. This protein forms a heterodimer with BCL2, and functions as an apoptotic activator. This protein is reported to interact with, and increase the opening of, the mitochondrial voltage-dependent anion channel (VDAC), which leads to the loss in membrane potential and the release of cytochrome c. The expression of this gene is regulated by the tumor suppressor P53 and has been shown to be involved in P53-mediated apoptosis.

<span class="mw-page-title-main">BH3 interacting-domain death agonist</span> Protein-coding gene in the species Homo sapiens

The BH3 interacting-domain death agonist, or BID, gene is a pro-apoptotic member of the Bcl-2 protein family. Bcl-2 family members share one or more of the four characteristic domains of homology entitled the Bcl-2 homology (BH) domains, and can form hetero- or homodimers. Bcl-2 proteins act as anti- or pro-apoptotic regulators that are involved in a wide variety of cellular activities.

<span class="mw-page-title-main">Bcl-2 homologous antagonist killer</span> Protein-coding gene in the species Homo sapiens

Bcl-2 homologous antagonist/killer is a protein that in humans is encoded by the BAK1 gene on chromosome 6. The protein encoded by this gene belongs to the BCL2 protein family. BCL2 family members form oligomers or heterodimers and act as anti- or pro-apoptotic regulators that are involved in a wide variety of cellular activities. This protein localizes to mitochondria, and functions to induce apoptosis. It interacts with and accelerates the opening of the mitochondrial voltage-dependent anion channel, which leads to a loss in membrane potential and the release of cytochrome c. This protein also interacts with the tumor suppressor P53 after exposure to cell stress.

<span class="mw-page-title-main">Bcl-2-associated death promoter</span> Mammalian protein found in Homo sapiens

The BCL2 associated agonist of cell death (BAD) protein is a pro-apoptotic member of the Bcl-2 gene family which is involved in initiating apoptosis. BAD is a member of the BH3-only family, a subfamily of the Bcl-2 family. It does not contain a C-terminal transmembrane domain for outer mitochondrial membrane and nuclear envelope targeting, unlike most other members of the Bcl-2 family. After activation, it is able to form a heterodimer with anti-apoptotic proteins and prevent them from stopping apoptosis.

<span class="mw-page-title-main">Bcl-2-like protein 1</span> Protein-coding gene in the species Homo sapiens

Bcl-2-like protein 1 is a protein encoded in humans by the BCL2L1 gene. Through alternative splicing, the gene encodes both of the human proteins Bcl-xL and Bcl-xS.

<span class="mw-page-title-main">Diablo homolog</span> Protein-coding gene in the species Homo sapiens

Diablo homolog (DIABLO) is a mitochondrial protein that in humans is encoded by the DIABLO gene on chromosome 12. DIABLO is also referred to as second mitochondria-derived activator of caspases or SMAC. This protein binds inhibitor of apoptosis proteins (IAPs), thus freeing caspases to activate apoptosis. Due to its proapoptotic function, SMAC is implicated in a broad spectrum of tumors, and small molecule SMAC mimetics have been developed to enhance current cancer treatments.

<span class="mw-page-title-main">Dynamin-like 120 kDa protein</span> Protein-coding gene in the species Homo sapiens

Dynamin-like 120 kDa protein, mitochondrial is a protein that in humans is encoded by the OPA1 gene. This protein regulates mitochondrial fusion and cristae structure in the inner mitochondrial membrane (IMM) and contributes to ATP synthesis and apoptosis, and small, round mitochondria. Mutations in this gene have been implicated in dominant optic atrophy (DOA), leading to loss in vision, hearing, muscle contraction, and related dysfunctions.

<span class="mw-page-title-main">MFN1</span> Protein-coding gene in the species Homo sapiens

Mitofusin-1 is a protein that in humans is encoded by the MFN1 gene.

<span class="mw-page-title-main">GHITM</span> Protein-coding gene in the species Homo sapiens

Growth hormone-inducible transmembrane protein (GHITM), also known as transmembrane BAX inhibitor motif containing protein 5 (TMBIM5), is a protein that in humans is encoded by the GHITM gene on chromosome 10. It is a member of the BAX inhibitor motif containing (TMBIM) family and localizes to the inner mitochondrial membrane (IMM), as well as the endoplasmic reticulum (ER), where it plays a role in apoptosis through mediating mitochondrial morphology and cytochrome c release. Through its apoptotic function, GHITM may be involved in tumor metastasis and innate antiviral responses.

<span class="mw-page-title-main">Mitochondrial apoptosis-induced channel</span>

The mitochondrial apoptosis-induced channel, is an early marker of the onset of apoptosis. This ion channel is formed on the outer mitochondrial membrane in response to certain apoptotic stimuli. MAC activity is detected by patch clamping mitochondria from apoptotic cells at the time of cytochrome c release.

<span class="mw-page-title-main">YME1L1</span> Protein-coding gene in the species Homo sapiens

ATP-dependent metalloprotease YME1L1 is an enzyme that in humans is encoded by the YME1L1 gene. YME1L1 belongs to the AAA family of ATPases and mainly functions in the maintenance of mitochondrial morphology. Mutations in this gene would cause infantile-onset mitochondriopathy.

<span class="mw-page-title-main">PARL</span> Protein-coding gene in the species Homo sapiens

Presenilins-associated rhomboid-like protein, mitochondrial (PSARL), also known as PINK1/PGAM5-associated rhomboid-like protease (PARL), is an inner mitochondrial membrane protein that in humans is encoded by the PARL gene on chromosome 3. It is a member of the rhomboid family of intramembrane serine proteases. This protein is involved in signal transduction and apoptosis, as well as neurodegenerative diseases and type 2 diabetes.

<span class="mw-page-title-main">ADP/ATP translocase 4</span> Protein-coding gene in the species Homo sapiens

ADP/ATP translocase 4 (ANT4) is an enzyme that in humans is encoded by the SLC25A31 gene on chromosome 4. This enzyme inhibits apoptosis by catalyzing ADP/ATP exchange across the mitochondrial membranes and regulating membrane potential. In particular, ANT4 is essential to spermatogenesis, as it imports ATP into sperm mitochondria to support their development and survival. Outside this role, the SLC25AC31 gene has not been implicated in any human disease.

<span class="mw-page-title-main">VDAC2</span> Protein-coding gene in the species Homo sapiens

Voltage-dependent anion-selective channel protein 2 is a protein that in humans is encoded by the VDAC2 gene on chromosome 10. This protein is a voltage-dependent anion channel and shares high structural homology with the other VDAC isoforms. VDACs are generally involved in the regulation of cell metabolism, mitochondrial apoptosis, and spermatogenesis. Additionally, VDAC2 participates in cardiac contractions and pulmonary circulation, which implicate it in cardiopulmonary diseases. VDAC2 also mediates immune response to infectious bursal disease (IBD).

<span class="mw-page-title-main">Bcl-2 family</span>

The Bcl-2 family consists of a number of evolutionarily-conserved proteins that share Bcl-2 homology (BH) domains. The Bcl-2 family is most notable for their regulation of apoptosis, a form of programmed cell death, at the mitochondrion. The Bcl-2 family proteins consists of members that either promote or inhibit apoptosis, and control apoptosis by governing mitochondrial outer membrane permeabilization (MOMP), which is a key step in the intrinsic pathway of apoptosis. A total of 25 genes in the Bcl-2 family were identified by 2008.

<span class="mw-page-title-main">Mitochondrial fusion</span> Merging of two or more mitochondria within a cell to form a single compartment

Mitochondria are dynamic organelles with the ability to fuse and divide (fission), forming constantly changing tubular networks in most eukaryotic cells. These mitochondrial dynamics, first observed over a hundred years ago are important for the health of the cell, and defects in dynamics lead to genetic disorders. Through fusion, mitochondria can overcome the dangerous consequences of genetic malfunction. The process of mitochondrial fusion involves a variety of proteins that assist the cell throughout the series of events that form this process.

References

  1. ↑ "Luca Scorrano". Google Scholar . Retrieved 9 December 2013.
  2. ↑ Scorrano, Luca; Ashiya, Mona; Buttle, Karolyn; Weiler, Solly; Oakes, Scott A.; Mannella, Carmen A.; Korsmeyer, Stanley J. (January 2002). "A distinct pathway remodels mitochondrial cristae and mobilizes cytochrome c during apoptosis". Developmental Cell. 2 (1): 55–67. doi: 10.1016/s1534-5807(01)00116-2 . ISSN   1534-5807. PMID   11782314.
  3. ↑ Cipolat, Sara; Rudka, Tomasz; Hartmann, Dieter; Costa, Veronica; Serneels, Lutgarde; Craessaerts, Katleen; Metzger, Kristine; Frezza, Christian; Annaert, Wim; D'Adamio, Luciano; Derks, Carmen (14 July 2006). "Mitochondrial rhomboid PARL regulates cytochrome c release during apoptosis via OPA1-dependent cristae remodeling". Cell. 126 (1): 163–175. doi: 10.1016/j.cell.2006.06.021 . ISSN   0092-8674. PMID   16839884. S2CID   6396519.
  4. ↑ Scorrano, Luca; Ashiya, Mona; Buttle, Karolyn; Weiler, Solly; Oakes, Scott A.; Mannella, Carmen A.; Korsmeyer, Stanley J. (January 2002). "A distinct pathway remodels mitochondrial cristae and mobilizes cytochrome c during apoptosis". Developmental Cell. 2 (1): 55–67. doi: 10.1016/s1534-5807(01)00116-2 . ISSN   1534-5807. PMID   11782314.
  5. ↑ Frezza, Christian; Cipolat, Sara; Martins de Brito, Olga; Micaroni, Massimo; Beznoussenko, Galina V.; Rudka, Tomasz; Bartoli, Davide; Polishuck, Roman S.; Danial, Nika N.; De Strooper, Bart; Scorrano, Luca (14 July 2006). "OPA1 controls apoptotic cristae remodeling independently from mitochondrial fusion". Cell. 126 (1): 177–189. doi: 10.1016/j.cell.2006.06.025 . ISSN   0092-8674. PMID   16839885. S2CID   11569831.
  6. ↑ Cipolat, Sara; Martins de Brito, Olga; Dal Zilio, Barbara; Scorrano, Luca (9 November 2004). "OPA1 requires mitofusin 1 to promote mitochondrial fusion". Proceedings of the National Academy of Sciences of the United States of America. 101 (45): 15927–15932. doi: 10.1073/pnas.0407043101 . ISSN   0027-8424. PMC   528769 . PMID   15509649.
  7. ↑ Frezza, Christian; Cipolat, Sara; Martins de Brito, Olga; Micaroni, Massimo; Beznoussenko, Galina V.; Rudka, Tomasz; Bartoli, Davide; Polishuck, Roman S.; Danial, Nika N.; De Strooper, Bart; Scorrano, Luca (14 July 2006). "OPA1 controls apoptotic cristae remodeling independently from mitochondrial fusion". Cell. 126 (1): 177–189. doi: 10.1016/j.cell.2006.06.025 . ISSN   0092-8674. PMID   16839885. S2CID   11569831.
  8. ↑ Cogliati, Sara; Frezza, Christian; Soriano, Maria Eugenia; Varanita, Tatiana; Quintana-Cabrera, Ruben; Corrado, Mauro; Cipolat, Sara; Costa, Veronica; Casarin, Alberto; Gomes, Ligia C.; Perales-Clemente, Ester (26 September 2013). "Mitochondrial cristae shape determines respiratory chain supercomplexes assembly and respiratory efficiency". Cell. 155 (1): 160–171. doi:10.1016/j.cell.2013.08.032. ISSN   1097-4172. PMC   3790458 . PMID   24055366.
  9. ↑ Civiletto, Gabriele; Varanita, Tatiana; Cerutti, Raffaele; Gorletta, Tatiana; Barbaro, Serena; Marchet, Silvia; Lamperti, Costanza; Viscomi, Carlo; Scorrano, Luca; Zeviani, Massimo (2 June 2015). "Opa1 overexpression ameliorates the phenotype of two mitochondrial disease mouse models". Cell Metabolism. 21 (6): 845–854. doi:10.1016/j.cmet.2015.04.016. ISSN   1932-7420. PMC   4457891 . PMID   26039449.
  10. ↑ Varanita, Tatiana; Soriano, Maria Eugenia; Romanello, Vanina; Zaglia, Tania; Quintana-Cabrera, Rubén; Semenzato, Martina; Menabò, Roberta; Costa, Veronica; Civiletto, Gabriele; Pesce, Paola; Viscomi, Carlo (2 June 2015). "The OPA1-dependent mitochondrial cristae remodeling pathway controls atrophic, apoptotic, and ischemic tissue damage". Cell Metabolism. 21 (6): 834–844. doi:10.1016/j.cmet.2015.05.007. ISSN   1932-7420. PMC   4457892 . PMID   26039448.
  11. ↑ Frezza, Christian; Cipolat, Sara; Martins de Brito, Olga; Micaroni, Massimo; Beznoussenko, Galina V.; Rudka, Tomasz; Bartoli, Davide; Polishuck, Roman S.; Danial, Nika N.; De Strooper, Bart; Scorrano, Luca (14 July 2006). "OPA1 controls apoptotic cristae remodeling independently from mitochondrial fusion". Cell. 126 (1): 177–189. doi: 10.1016/j.cell.2006.06.025 . ISSN   0092-8674. PMID   16839885. S2CID   11569831.
  12. ↑ Gomes, Ligia C.; Di Benedetto, Giulietta; Scorrano, Luca (May 2011). "During autophagy mitochondria elongate, are spared from degradation and sustain cell viability". Nature Cell Biology. 13 (5): 589–598. doi:10.1038/ncb2220. ISSN   1476-4679. PMC   3088644 . PMID   21478857.
  13. ↑ Kasahara, Atsuko; Cipolat, Sara; Chen, Yun; Dorn, Gerald W.; Scorrano, Luca (8 November 2013). "Mitochondrial fusion directs cardiomyocyte differentiation via calcineurin and Notch signaling". Science. 342 (6159): 734–737. doi: 10.1126/science.1241359 . ISSN   1095-9203. PMID   24091702. S2CID   20355613.
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